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Research and Reporting Methods |

A Review of the Evidence for Overlap among Unexplained Clinical Conditions

Leslie A. Aaron, PhD, MPH; and Dedra Buchwald, MD
[+] Article and Author Information

Copyright ©2004 by the American College of Physicians

Acknowledgments: The authors thank Drs. Kurt Kroenke and Jack Goldberg for their helpful comments on several versions of this paper.

Requests for Single Reprints: Leslie Aaron, PhD, MPH, Department of Medicine, Division of Internal Medicine, Harborview Medical Center, 325 Ninth Avenue, Box 359780, Seattle, WA 98104; e-mail, laaron@u.washington.edu.

Current Author Addresses: Drs. Aaron and Buchwald: Department of Medicine, Division of Internal Medicine, Harborview Medical Center, 325 Ninth Avenue, Box 359780, Seattle, WA 98104.


Ann Intern Med. 2001;134(9_Part_2):868-881. doi:10.7326/0003-4819-134-9_Part_2-200105011-00011
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Purpose: Unexplained clinical conditions share features, including symptoms (fatigue, pain), disability out of proportion to physical examination findings, inconsistent demonstration of laboratory abnormalities, and an association with “stress” and psychosocial factors. This literature review examines the nature and extent of the overlap among these unexplained clinical conditions and the limitations of previous research.

Data Sources: English-language articles were identified by a search of the MEDLINE database from 1966 to January 2001 by using individual syndromes and their hallmark symptoms as search terms.

Study Selection: Studies that assessed patients with at least one unexplained clinical condition and that included information on symptoms, overlap with other unexplained clinical conditions, or physiologic markers. Conditions examined were the chronic fatigue syndrome, fibromyalgia, the irritable bowel syndrome, multiple chemical sensitivity, temporomandibular disorder, tension headache, interstitial cystitis, and the postconcussion syndrome.

Data Extraction: Information on authorship, patient and control groups, eligibility criteria, case definitions, study methods, and major findings.

Data Synthesis: Many similarities were apparent in case definition and symptoms, and the proportion of patients with one unexplained clinical condition meeting criteria for a second unexplained condition was striking. Tender points on physical examination and decreased pain threshold and tolerance were the most frequent and consistent objective findings. A major shortcoming of all proposed explanatory models is their inability to account for the occurrence of unexplained clinical conditions in many affected patients.

Conclusions: Overlap between unexplained clinical conditions is substantial. Most studies are limited by methodologic problems, such as case definition and the selection and recruitment of case-patients and controls.

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